期刊
AMINO ACIDS
卷 50, 期 10, 页码 1471-1483出版社
SPRINGER WIEN
DOI: 10.1007/s00726-018-2625-4
关键词
Pseudomonas aeruginosa; Antimicrobial peptides; Analogs; Multidrug-resistant bacteria; Anti-biofilm
资金
- National Natural Science Foundation of China [81602945, 81673283, 81473095]
- Program for Ministry of Education Peptide Drugs Innovation Team [IRT_15R27]
- China Postdoctoral Science Foundation [2016M592593]
- Fundamental Research Funds for the Central Universities [lzujbky-2017-k11, lzujbky-2017-119, lzujbky-2017-139]
Pseudomonas aeruginosa is particularly difficult to treat because it possesses a variety of resistance mechanisms and because it often forms biofilms. Antimicrobial peptides represent promising candidates for future templates of antibiotic-resistant bacterial infections due to their unique mechanism of antimicrobial action. In this study, we first found that the antimicrobial peptide Feleucin-K3 has potent antimicrobial activity against not only the standard strain of P. aeruginosa but also against the multidrug-resistant strains isolated from clinics. Then, the structure-activity relationship of the peptide was investigated using alanine and D-amino acid scanning. Among the analogs synthesized, FK-1D showed much more potent antimicrobial activity, superior stability, and very low toxicity, and it was able to permeabilize bacterial membranes. Furthermore, it exhibited significant anti-biofilm activity. More importantly, FK-1D showed excellent antimicrobial activity in vivo, especially against clinical multidrug-resistant bacteria, in contrast to ceftazidime. Our results suggested that FK-1D could be subjected to fixed-point modification in the first and fourth sites to further optimize its medicinal properties and potential as a lead compound for the treatment of infections caused by multidrug-resistant P. aeruginosa and the associated biofilms.
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